Effects of isoxazolo-pyridinone 7e, a potent activator of the Nurr1 signaling pathway, on experimental autoimmune encephalomyelitis in mice

• Published in: PloS one Vol. 9; no. 9; p. e108791
• Main Authors: Montarolo, Francesca, Raffaele, Chiara, Perga, Simona, Martire, Serena, Finardi, Annamaria, Furlan, Roberto, Hintermann, Samuel, Bertolotto, Antonio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29-09-2014; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Axons - drug effects; Axons - metabolism; Axons - pathology; Biology and Life Sciences; Brain; Cell Count; Central nervous system; Chronic illnesses; Demyelinating Diseases - complications; Demyelinating Diseases - drug therapy; Demyelinating Diseases - pathology; Demyelination; Disease prevention; Dopamine; Down-Regulation - drug effects; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - complications; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental allergic encephalomyelitis; Female; Gene expression; Inflammation; Isoxazoles - administration & dosage; Isoxazoles - pharmacology; Isoxazoles - therapeutic use; Leukocytes (mononuclear); Lymphocytes; Macrophages - drug effects; Mice, Inbred C57BL; Multiple sclerosis; Myelin-Oligodendrocyte Glycoprotein; Nervous system; Neurobiology; Neurodegeneration; Neurology; Neurosciences; NF-kappa B - metabolism; NF-κB protein; Nuclear Receptor Subfamily 4, Group A, Member 2 - metabolism; Nuclear receptors; Nurr1 protein; Oxazoles - administration & dosage; Oxazoles - pharmacology; Oxazoles - therapeutic use; Peptide Fragments; Peripheral blood mononuclear cells; Pyrimidinones - administration & dosage; Pyrimidinones - pharmacology; Pyrimidinones - therapeutic use; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; T cell receptors; T-Lymphocytes - drug effects; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108791

Multiple sclerosis (MS) is an autoimmune chronic disease of the central nervous system (CNS) characterized by immune-mediated inflammation, demyelination and subsequent axonal damage. Gene expression profiling showed that Nurr1, an orphan nuclear receptor, is down-regulated in peripheral blood mononuclear cells of MS patients. Nurr1 exerts an anti-inflammatory role repressing the activity of the pro-inflammatory transcription factor NF-kB. Here, we report that the preventive treatment with isoxazolo-pyridinone 7e, an activator of Nurr1 signaling pathway, reduces the incidence and the severity of a MS murine model, i.e. experimental autoimmune encephalomyelitis (EAE). The compound is able to attenuate inflammation and neurodegeneration in spinal cords of EAE mice by an NF-kB pathway-dependent process.